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Updated: Aug 6, 2026
Preterm EEG: A Multimodal Neurophysiological Protocol
Published on: February 18, 2012
Bilirubin and serial auditory brainstem responses in premature infants
S B Amin1, C Ahlfors, M S Orlando
1Department of Pediatrics, Division of Neonatology, Children's Hospital at Strong, Rochester, New York, USA. sanamin@aol.com
Insights
Unbound bilirubin (UB) is a better predictor of bilirubin encephalopathy in premature infants than total bilirubin or the bilirubin-albumin ratio. Higher UB levels significantly correlate with abnormal auditory brainstem responses, indicating potential neurological impact.
Area of Science:
- Neonatal Medicine
- Neuroscience
- Biochemistry
Background:
- Hyperbilirubinemia is common in premature infants (28-32 weeks' gestational age).
- Assessing the risk of bilirubin encephalopathy is crucial for timely intervention.
- Traditional markers like total serum bilirubin (TB) may not fully capture the risk.
Purpose of the Study:
- To evaluate unbound bilirubin (UB) and bilirubin-albumin molar ratio (B:A MR) as predictors of bilirubin encephalopathy.
- To compare their efficacy against serum total bilirubin (TB).
- To assess prediction using auditory brainstem responses (ABR) in preterm neonates.
Main Methods:
- Serial ABRs were performed on 143 preterm infants during the first postnatal week.
- ABR maturation was categorized as normal or abnormal based on waveform and latency.
- Serum albumin, TB, and UB were analyzed at specific postnatal intervals.
Main Results:
- Peak TB levels did not differ significantly between infants with normal and abnormal ABR maturation.
- Peak UB levels were significantly higher in infants with abnormal ABR maturation.
- A UB level of 0.5 microg/dL demonstrated 70% sensitivity and 75% specificity for predicting abnormal ABR maturation.
Conclusions:
- Unbound bilirubin (UB) is a more sensitive predictor of abnormal ABR maturation than TB or B:A MR.
- UB effectively identifies preterm infants at higher risk for transient bilirubin encephalopathy.
- These findings support the clinical utility of UB monitoring in neonatal hyperbilirubinemia management.
Objectives:
To determine the usefulness of the bilirubin-albumin (B:A) molar ratio (MR) and unbound bilirubin (UB) as compared with serum total bilirubin (TB) in predicting bilirubin encephalopathy as assessed by auditory brainstem responses (ABR) in infants of 28 to 32 weeks' gestational age.
Study Design:
During a 2-year period, serial ABRs were obtained on 143 infants of 28 to 32 weeks' gestational age during the first postnatal week. Waveforms were categorized on the basis of response replicability and the presence of waves III and V. Wave V latencies were also serially analyzed when measurable for individual infants. Maturation of the ABR was defined as abnormal when the waveform category worsened and/or latency increased during the study interval. Serum albumin was analyzed at 48 to 72 hours of age in all patients. Serum TB was analyzed as clinically indicated. Aliquots of the same samples were also analyzed for UB in a subset of infants.
Results:
The mean peak TB concentration (10.1 +/- 1.7 mg/dL) for the 71 infants with normal ABR maturation was not significantly different from the mean peak TB (10.2 +/- 2.1 mg/dL) in the 24-hour period preceding the ABR's first showing abnormal maturation in the other 55 infants. However, in infants with UB analyzed, the mean peak UB (0.62 +/- 0.20 vs 0.40 +/- 0.15 microg/dL) was significantly higher in the infants with abnormal maturation (n = 25) than in infants with normal maturation (n = 20). The B:A MR results were equivocal. In the entire study population, there was no difference in B:A MR between infants with normal versus abnormal ABR maturation. However, in the subset of infants in whom UB was measured, although TB was not different, there was a significant difference in B:A MR. Based on receiver-operating characteristic curves, a UB level of 0.5 microg/dL was the best discriminator with a sensitivity of 70% and a specificity of 75%. The proportion of infants who had UB >0.5 microg/dL and UB 0.5 microg/dL compared with UB
Conclusions:
UB is a more sensitive predictor than either serum bilirubin or B:A MR of abnormal ABR maturation, and hence transient bilirubin encephalopathy in premature newborns with hyperbilirubinemia.
